With an estimated annual incidence of 300,000-350,000 and accounting for 50% of all cardiovascular deaths in the US, sudden cardiac death (SCD) is a condition with significant implications for public health. Despite ongoing treatment advances in resuscitation science, survival among out-of-hospital cardiac arrest victims is <10%, making SCD prediction and prevention essential. While SCD risk is strongly associated with increasing age, manifestation in middle age (35-59 yr; approx. 30% of all SCD) is the most significant contributor to societal burden. However, published studies of SCD have focused almost exclusively on older patients (?60 yr), partly explained by insufficient numbers of middle-aged SCD cases among existing cardiovascular cohort studies. We have recently reported evidence for a distinctive profile of SCD in middle age compared to older age, indicating the significance of identifying middle age-specific SCD mechanisms. Middle aged SCD patients were more likely to present without prior warning, with obesity and non-white race playing a more important role. The overall hypothesis of this proposal is that a detailed and focused examination of novel factors associated with SCD in middle age will enhance the understanding of mechanisms and contribute to improved SCD risk prediction and prevention. Our specific aims are 1) To identify features of malignant coronary events that provoke lethal arrhythmias in middle age 2) To identify novel obesity-related risk factors contributing to SCD risk; and 3) To identify patient subgroups at highest risk of SCD in middle age. Over twelve years ago, we initiated the Oregon Sudden Unexpected Death Study (Oregon SUDS) to identify novel risk predictors for SCD. This large study among one million residents of the Portland, Oregon metro area continues to accrue a significant number of SCD cases and controls. The critical need to identify risk predictors for SCD in middle age currently represents the largest knowledge gap in SCD. The established Oregon SUDS provides a unique discovery population with sufficient numbers of subjects, coupled with the opportunity to leverage existing detailed clinical and biomarker information. There is a high likelihood of identifying clinically and mechanistically relevant predictors of SCD risk that will enhance prediction and prevention of SCD.